Daily Archives: January 26, 2015

Patient Presentation A 12-year-old female came to clinic for her health maintenance examination. She had no complaints and her mother had no concerns until her daughter was weighed and there was a slower increase in her weight over the year. The patient had normal eating and activity and they denied weight loss. She was sleeping well without night sweats, had normal elimination and was doing well in school. She had a history of being a more anxious child but this was unchanged. The family also denied any skin or hair changes. The past medical history was negative except for some normal acute illnesses. The family history was positive for diabetes, stroke and arthritis. The review of systems was otherwise normal.

The pertinent physical exam showed a well-appearing Asian female with a heart rate of 108 beats/minute, blood pressure of 106/56, respiratory rate of 20 and she was afebrile. Her height was 90% and tracking normally. Her weight had always been at the 95% and was now at the 90%. HEENT revealed very subtle proptosis with the eyelids still covering part of the irises. Her thyroid was diffusely enlarged without palpable nodes and there was no murmur over the organ. She had some shoddy anterior cervical adenopathy. Heart was mildly tachycardic without a murmur. She had normal skin without hair loss or increased perspiration. Neurological examination found a mild tremor of her hands when they were outstretched and she seemed somewhat anxious to the examiner. She also had mild hyperreflexia in all extremities. The laboratory evaluation showed a thyroid stimulating hormone of < 0.1 microU/mL (normal 0.5-4.7 microU/mL), and a free T4 of 3.9 ng/dL (normal 0.8-2.7 ng/dL).

The diagnosis of hyperthyroidism with thyrotoxicosis was made and pediatric endocrinology was consulted by telephone. An appointment for evaluation was made for 2 days later. The radiologic evaluation of a thyroid ultrasound found a mildly diffusely enlarged organ without nodules. Additional laboratory testing was positive for TSH receptor antibodies consistent with Grave’s disease. She began treatment with the antithyroid drug methimazole.

Discussion

The thyroid gland secrets two hormones – T4 which is a prohormone and T3 which is the biologically active hormone. Receptors for T3 are found in nearly all body tissues. T3 regulates metabolism and energy production. Organs most affected are the heart, liver and central nervous system as well as growth of the fetus and child. Hyperthyroidism is common with a prevalence rate of about 1-2% for women and 0.2% for men. The most common cause of thyrotoxicosis is Grave’s disease where autoantibodies to thyroid stimulating hormone (TSH) exist. These autoantibodies attach to thyroid tissue TSH receptors and increase the production of T4 and T3. Grave’s disease often co-occurs with other autoimmune diseases such as diabetes, Hashimoto’s thyroiditis, rheumatoid arthritis and also with Turner’s, Down’s and Di George syndromes. Children only account for about 1-2% of all patients with Grave’s disease.

Antithyroid drugs (ATD) – The most common drugs used are carbimazole and its active metabolite methimazole (MMI) and propylthiouracil. Propylthiouracil is usually not used because of the risk of severe hepatitis.
MMI is the most common first line drug used and is taken orally daily. Side effects include hives, rashes, gastrointestinal problems and arthritis.
The goal is to create a euthyroidism condition which then stops the autoimmune response and the thyrotoxicosis. This is defined as the clinical remission.

Radioactive iodine (RAI) – it is often used as a more radical treatment if clinical remission cannot be obtained or sustained with ATDs. It may be used as a first line treatment for patients with a large goiter or opthalmopathy.
A single dose if often used, but the patient may need additional treatments. It is not used in young children, or pregnant or lactating mothers because of the potential risk of neoplasia.

Surgery – total or near total thyroidectomy is the most common surgery. RAI may be needed if hyperthyroidism continues after surgery. Surgery causes hypothyroidism and the need for lifelong replacement thyroid medication.

Learning Point
Only about 30% of children achieve clinical remission with ATD treatment, whereas 60-70% of adults achieve remission.
Longer term ATD may be necessary to achieve and keep children in clinical remission. If remission cannot be achieved or sustained, then other treatment is necessary.

Favorable predictors of Grave’s disease remission are older age group, presence of other autoimmune conditions and duration of ATD treatment more than 2 years.
Unfavorable predictors are younger age, large goiter, non-Caucasian race, biochemical severity and ATD medication non-compliance.

Questions for Further Discussion
1. How is Hashimoto’s thyroiditis different from Grave’s Disease?
2. What causes thyrotoxicosis?

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